We investigated the efficacy of fluconazole on experimental disseminated candidiasis in mice immunocompromised by chronic morphine treatment. CD1 mice were severely immunosuppressed by repeated morphine administrations, i.e., subcutaneous (s.c.) injections of 75 mg/kg/day, 3 days before and 5 days after a systemic Candida albicans infection induced by intravenous administration of 1 x 10(6) fungal cells/mouse. Fluconazole (2.5 mg/kg, s.c., at 6, 24 and 48 h postinfection) was very effective in prolonging survival time of morphine-treated mice. Fluconazole treatment also promotes a recovery of killing activity of polymorphonuclear leukocyte cells suppressed by morphine administrations.

Animals↗

PubMedDate not supplied

Macrophages: a crucial reservoir for human immunodeficiency virus in the body.

The replication of Human Immunodeficiency Virus (HIV) in cells of macrophage lineage represents a key pathogenetic event of the neurological damages typically found during the course of this disease. Macrophages are persistently infected cells and thus not susceptible to the cytophatic effect typical of infected activated CD4-lymphocytes. The resistance of macrophages to HIV infection is at least in part mediated by the autocrine production of the nerve growth factor (NGF), a neurokine able to sustain the survival of some cells of bone marrow origin, including monocyte-derived macrophages. This anti-apoptotic effect of NGF in HIV-infected macrophages can be even more relevant at the central nervous system level, where many cells are able to physiologically produce NGF, thus further increasing the survival of macrophages infected by HIV, and enhancing the damages that these cells may induce upon bystander neurons. The proapoptotic effect of soluble factors released by HIV-infected macrophages may heavily affect the survival and functions also of astrocytes, that in turn become unable to sustain neuronal homeostasis. Taken together, this information supports the importance of therapeutic attempts aimed at attacking virus replication in infected macrophages and/or to selectively eliminate these chronically infected and persistently virus-producing cells.

AIDS Dementia Complex↗

PubMedDate not supplied

Fluconazole resistance in Candida albicans: a review of mechanisms.

Antifungal agents have greatly contributed to the improvement of public health. Nevertheless, antifungal resistant pathogens have increased during the past decade, becoming a serious concern. Candida albicans has been the most extensively studied pathogen in antifungal resistance because of their morbidity and mortality associated with infections in immunocompromised patients. This review describes the antifungal mechanims of the azole fluconazole widely used for the prophylaxis and treatment of candidal infections. The specific molecular pathways occurring in fluconazole-resistance of C. albicans and some issues about new antifungal agents are also discussed.

Animals↗

PubMedDate not supplied

Mechanism of production of interferon-gamma: role of arachidonic acid metabolites.

The effects of arachidonic acid metabolites on mitogen-induced interferon (IFN)-gamma production by human peripheral blood mononuclear cells (PBMC) were examined. Both prostaglandins E2 (PGE2) and leukotrienes B4 (LTB4) were produced after macrophage activation stimulated by galactose oxidase (GO) and Staphylococcal enterotoxin B (SEB), two well known inducers of IFN-gamma. To test the involvement of PGE2 and LTB4 in IFN-gamma production, GO- and SEB-activated PBMC were treated with two inhibitors of cyclooxygenase (aspirin and indomethacin) and with an inhibitor of lipoxygenase [nordihydroguaiaretic acid (NDGA)]. The results of these experiments showed that aspirin and indomethacin cause a marked increase of IFN-gamma production by GO- and SEB-activated PBMC. On the contrary, NDGA treatment reduced IFN-gamma production induced by the same agents. Moreover, whereas the addition of exogenous PGE2 reduces IFN gamma production, the addition of exogenous LTB4 does not affect IFN-gamma production. Taken together these findings indicate that arachidonic acid metabolites, produced during mitogenic activation, are involved in the regulation of IFN-gamma production and suggest that, in our system, LTB4 exerts a positive modulating signal while PGE2 represents a negative signal.

5,8,11,14-Eicosatetraynoic Acid↗

PubMedDate not supplied